OSCR

Optimization of Pyrazole-Based Activators of Kv3.1.

Overview

Authors: Paul K Spearing1, Vaishali Satpute Janve2, Ian M Romaine3, Navoda Jayakodiarachchi1, Benjamin W Guttentag3, Somnath Jana1,3, Kwangho Kim1,3,4, Jerod S Denton2,3,4, Craig W Lindsley1,3,4,5, Alex G Waterson3,4,5
ORCID iDs: Benjamin W Guttentag, Craig W Lindsley, Alex G Waterson
  1. Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States
  2. Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
  3. Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States
  4. Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States
  5. Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, United States
Institutions: Vanderbilt University (United States); Vanderbilt University Medical Center (United States)
Journal: ACS medicinal chemistry letters, volume 17, issue 7, pages 1655-1663
Dates: received 18 May 2026; accepted 12 June 2026; published online 25 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1021/acsmedchemlett.6c00272 · PMID 42445039 · PMCID PMC13358987 · OpenAlex W7165856424
Open access: hybrid, a free copy (OpenAlex)
Status: data only
Categories: cellular / molecular (subfield)
Keywords: potassium channel, Kv3.1 activation, ion channel research, CNS drug discovery
Topic: Organic Light-Emitting Diodes Research (Electrical and Electronic Engineering, Engineering), according to OpenAlex
Funding: National Institute of Mental Health (1R01MH131721); NIMH NIH HHS (R01 MH131721); NIH HHS (S10 OD028715); NIH Shared Instrumentation Grant (1S10OD028715); William K. Warren Family and Foundation
Citations: not cited yet (Europe PMC); 33 references in the paper

Abstract

Potentiators of the Kv3.1 voltage-gated potassium channel may have utility as therapies for certain CNS disorders. A SAR survey around a previously reported Kv3.1 activator scaffold led to the identification of compounds with superior potency and higher activation levels than reported molecules. We further demonstrated that these compounds show relevant activity in a patch-clamp electrophysiology assay. Together, the defined tractability in the chemotype and the promising biological activity indicate that these compounds may be leads for continued optimization toward therapies for neurological disorders.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 4 keywords, 5 funders, 31 references.

Cite

This paper

Spearing, P. K., Satpute Janve, V., Romaine, I. M., Jayakodiarachchi, N., Guttentag, B. W., Jana, S., Kim, K., Denton, J. S., Lindsley, C. W., & Waterson, A. G. (2026). Optimization of Pyrazole-Based Activators of Kv3.1. ACS medicinal chemistry letters, 17(7), 1655-1663. https://doi.org/10.1021/acsmedchemlett.6c00272

BibTeX

@article{spearing2026optimization,
author = {Spearing, Paul K and Satpute Janve, Vaishali and Romaine, Ian M and Jayakodiarachchi, Navoda and Guttentag, Benjamin W and Jana, Somnath and Kim, Kwangho and Denton, Jerod S and Lindsley, Craig W and Waterson, Alex G},
title = {{Optimization of Pyrazole-Based Activators of Kv3.1}},
journal = {ACS medicinal chemistry letters},
year = {2026},
month = jun,
volume = {17},
number = {7},
pages = {1655--1663},
publisher = {American Chemical Society},
issn = {1948-5875},
doi = {10.1021/acsmedchemlett.6c00272},
url = {https://doi.org/10.1021/acsmedchemlett.6c00272},
pmid = {42445039},
pmcid = {PMC13358987}
}

RIS

TY - JOUR
AU - Spearing, Paul K
AU - Satpute Janve, Vaishali
AU - Romaine, Ian M
AU - Jayakodiarachchi, Navoda
AU - Guttentag, Benjamin W
AU - Jana, Somnath
AU - Kim, Kwangho
AU - Denton, Jerod S
AU - Lindsley, Craig W
AU - Waterson, Alex G
TI - Optimization of Pyrazole-Based Activators of Kv3.1
T2 - ACS medicinal chemistry letters
J2 - ACS Med Chem Lett
PY - 2026
DA - 2026/06/25
VL - 17
IS - 7
SP - 1655
EP - 1663
SN - 1948-5875
PB - American Chemical Society
DO - 10.1021/acsmedchemlett.6c00272
UR - https://doi.org/10.1021/acsmedchemlett.6c00272
LA - en
ER -

CSL-JSON

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